PRACTICAL PHARMACOLOGY PEER REVIEWED

PRACTICAL PHARMACOLOGY

Local Anesthetic Agents

in Companion Animal
Veterinary Practice
Michelle Ting Hoon, BVSc, MANZCVS, Shaun Pratt, BVSc, and Wendy Goodwin, PhD, BVSc, FANZCVS
University of Queensland School of Veterinary Science, Gatton, Australia

Local anesthetic (LA) agents work by reversibly
inhibiting nerve impulse conduction and produce
locoregional anesthesia through local tissue
desensitization. LA agents are inexpensive, are widely
available, improve anesthetic quality, contribute to
multimodal analgesia, and have opioid-sparing benefits
when used effectively. It is therefore important for
veterinary professionals across all disciplines to
understand how LA agents work and the risks for
toxicity.
Commonly used LA agents in small animal veterinary
practice include lidocaine, prilocaine, mepivacaine,
ropivacaine, and bupivacaine. They are available in
injectable and topical formulations and may be
combined with vasoactive additives such as
epinephrine. This article provides general indications
and risks associated with LA agent use. Technical
information on peripheral nerve blocks and a detailed
description of advanced routes of LA agent
administration are published elsewhere.1,2
MECHANISM OF ACTION AND
PHARMACOLOGIC PROPERTIES
The time to onset, duration of action, and risk for
toxicity vary between formulations and largely depend
on the pKa (the negative log of the acid dissociation
constant [Ka]), protein binding, and lipid solubility of
the LA agent.2 These physiochemical properties are
shown in TABLE 1 for common LA agents. In general,
LA agents reversibly bind to voltage-gated sodium
channels on the cell membrane of nerve axons to
prevent the influx of sodium ions. Consequently, the
initiation and propagation of action potentials are
inhibited, resulting in a reversible interruption to
nociceptive conduction and thus blocking transmission
of pain impulses (FIGURE 1).
Try_my_best/shutterstock.com

Abstract
Local anesthetic (LA) agents are an important part of multimodal analgesic protocols in veterinary practice. This
article provides an overview of commonly used LA agents and their indications and recommended doses, as well as
steps to prevent local anesthetic systemic toxicity.

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 PEER REVIEWED PRACTICAL PHARMACOLOGY

Take-Home Points
ƒ Local anesthetic (LA) agents
work by reversibly inhibiting
nerve impulse conduction.
ƒ LA agents are inexpensive
and widely available, improve
anesthetic quality, contribute to
multimodal analgesia, and have
opioid-sparing benefits.
ƒ Several steps can be taken
to avoid local anesthetic
systemic toxicity, including
adhering to maximum dose
recommendations, being aware
that drug absorption varies
between injection sites, and
avoiding mixing LA agents.
ƒ Lidocaine can be used
intravenously in dogs to provide
systemic analgesia, ventricular
antiarrhythmia treatment,
and multiorgan dysfunction
attenuation.

Susceptibility to LA agents varies between types of
nerves. Briefly, narrow-diameter myelinated sensory
fibers (classified as Aδ) and nerves of the autonomic
nervous system are more susceptible to LA agents than
larger-diameter pressure fibers (Aβ), motor fibers (Aα),
and unmyelinated chronic pain fibers. This explains
why a differential block between sensory and motor
nerve groups can be appreciated following the injection
of many LA agents.
The time to onset of an LA agent depends on the
agent’s ability to penetrate the nerve cell, as LA agents
bind to the internal aspect of the transmembrane
sodium channel (FIGURE 1). The duration of action is
determined by affinity for the sodium channel and
overall lipid solubility. The toxicity of LA agents is
determined by accumulation within cardiomyocytes
and cells of the central nervous system (TABLE 1).
Detailed descriptions of the physiochemical properties
of LA agents and how these affect their
pharmacokinetic properties are published elsewhere.1,4
ROUTES OF ADMINISTRATION
Locoregional anesthesia using LA agents can be
achieved by topical application, local infiltration into
tissues (e.g., subcutaneous infiltration, incisional line
block, wound diffusion catheters, splash blocks) and
cavities (intrasynovial and intra-articular), intravenous
local or regional anesthesia (Bier block), or targeted
peripheral perineural (nerve block) and central
neuraxial (epidural and subarachnoid) injections.
Additionally, some LA agents, such as lidocaine, can be
administered systemically via intravenous route for
acute perioperative pain management and to aid in the
treatment of certain cardiac arrhythmias in dogs.
LOCAL ANESTHETIC
SYSTEMIC TOXICITY
Central nervous system and cardiovascular disturbances
are the most common adverse effects associated with
local anesthetic systemic toxicity (LAST) and usually
result from inadvertent IV injection, rapid systemic
absorption, or absolute overdosing. Allergic reactions
may also occur. Central nervous system signs usually
appear first and include sedation, muscle tremors, and/
or seizures. The cardiovascular effects usually follow
and result from direct blockade of myocardial sodium
channels. This causes bradyarrhythmia and reduced
myocardial contractility; however, immediate
sympatholysis and vasodilation can be seen following

TABLE 1 Physiochemical Properties of Commonly Used Local Anesthetic Agentsa

PROTEIN
LOCAL ONSET TIME BINDING DURATION LIPID
ANESTHETIC pKa (MIN) (%) (MIN) SOLUBILITY TOXICITY RISK

Lidocaine 7.9 5 70 60–120 366 Low

Prilocaine 7.7 5 55 60–90 129 Low

Mepivacaine 7.6 10 75 90–120 130 Low

Ropivacaine 8.1 20 95 360–480 775 Medium

Bupivacaine 8.1 20 95 360–480 3420 High

a
The duration of action for the local anesthetic (LA) agents listed above should serve as a guide only. If perioperative analgesia relies on locoregional
anesthesia provided by an LA agent, routine patient pain scoring is recommended.3 pKa = negative log of the acid dissociation constant (Ka)

todaysveterinarypractice.com MAY/JUNE 2023 27

 PRACTICAL PHARMACOLOGY PEER REVIEWED

neuraxial anesthesia. Bupivacaine binds to the sodium
channel with greater affinity than lidocaine or
ropivacaine and dissociates more slowly, ultimately
resulting in prolonged conduction and reentry-induced
arrhythmias.1
In cases of tremors or seizures, intravenous volume
expansion, supportive care, and standard use of
antiepileptic drugs are indicated. Intubation,
ventilation, and oxygenation may be required. In cases
of cardiopulmonary arrest following suspected LAST,
intravenous lipid emulsion (ILE) has been shown to
improve survival when used in combination with
standard cardiopulmonary resuscitation.5 The rapid rise
in lipemia is thought to reduce active LA agent in the
blood and tissues. Increases in free fatty acids available
to the myocardium for oxidative phosphorylation may
also contribute. A loading dose of 1.5 to 2 mL/kg
followed by an infusion of 0.25 mL/kg/min of
commercially available 20% ILE has been used
successfully in dogs and cats to treat a range of
lipophilic toxicoses, including LAST. Constant rate
infusions (CRIs) have been maintained for 30 minutes
in cats and for up to 90 minutes in dogs.6,7
Considerations for ILE use include pancreatitis,
marked lipemia, lipid embolism, and allergic reactions.
A process known as ion trapping can occur in pregnant
animals, particularly during fetal distress. A reduction
in fetal pH increases the ionization of the LA agent in
the fetal circulation, leading to its accumulation. All LA
agents undergo this phenomenon to varying degrees.
Generally, the use of less toxic LA agents is
recommended in pregnant animals; administration of
IV doses of lidocaine is not recommended.
Prevention of LAST is paramount, and several steps can
be taken to reduce its risk:

Myelinated afferent
nerve fiber

LA

Dog: HeatherWolf/shutterstock.com; Syringe: Net Vector/shutterstock.com

H+ Na+
Voltage-gated
Na+ channel H+ Un-ionized
Na+ Ionized
LA LA
Extracellular
Na+

Intracellular

LA
LA H+
Na+

Action potential LA
generated, allowing pain H+
transmission H+

FIGURE 1. Mode of action of local anesthetic (LA) agents. Diffusion through the phospholipid bilayer of neurons depends on the
un-ionized concentration of the LA agent, which is determined by the pKa. In general, LA agents with a pKa similar to physiological
pH (7.4) rapidly diffuse into the cell and have faster onset times. For example, lidocaine (pKa 7.9) has a faster onset of action than
bupivacaine (pKa 8.1) because at a pH of 7.4 more of the drug is present in the un-ionized form.
H+ = hydrogen ion; NA+ = sodium ion; pKa = negative log of the acid dissociation constant (Ka).

28 MAY/JUNE 2023 todaysveterinarypractice.com


■ Aspirate prior to injection of the LA agent to avoid
inadvertent intravascular injection.
■ Adhere to maximum dose recommendations for the
specific agent and consider the physiologic status of
the individual patient. For example, neonates have
reduced liver metabolism and lower plasma protein
and thus are at an increased risk of LAST.
■ Consider concurrent use of vasoconstrictors (e.g.,
epinephrine) to reduce the systemic absorption of the
LA agent.
■ Take care when using multiple regional blocks in a
single patient and be aware that drug absorption varies
between injection sites. For example, high plasma
concentrations of LA agents occur with intercostal,
epidural, and brachial plexus blocks.
■ Avoid mixing LA agents, as the toxicity risk of
combining multiple agents is not known but should
be assumed to be additive (BOX 1).
■ In humans, international consensus guidelines on the
safety of IV lidocaine infusions exist and recommend
careful patient monitoring, slow administration of the
loading dose, not starting IV lidocaine within 4 hours
of regional nerve block (or vice versa), and continuing
the infusion for a maximum of 24 hours.10
COMMONLY USED AGENTS
Lidocaine Hydrochloride
Background: Commonly available as a 1% (10 mg/
mL) or 2% (20 mg/mL) hydrochloride solution
formulated alone or in combination with epinephrine.
Generally, lidocaine has a rapid onset and short
duration of action. The addition of local
vasoconstrictor agents (e.g., epinephrine, α2-receptor
agonists) can prolong lidocaine's duration of action and
inhibit the intrinsic local vasodilation.
Indications: Topical application onto cutaneous skin,
local infiltration into tissues or cavities, Bier block,
peripheral perineural injection, and central neuraxial
injection. Injectable formulations can be used
intravenously for their antiarrhythmic and analgesic
properties in dogs.
Recommended doses and safety: Subcutaneous and
peripheral perineural injections of up to 6 to 8 mg/kg
in dogs and 3 to 5 mg/kg in cats are generally
recommended. Topical spray products are registered for
use in cats to achieve laryngeal desensitization prior to
intubation; however, the authors recommend caution
in cats weighing less than 2 kg, given the relatively large
PEER REVIEWED PRACTICAL PHARMACOLOGY
BOX 1 Should Local Anesthetic
(LA) Agents Be Mixed?
It has been suggested that mixing
bupivacaine and lidocaine provides
the best of both worlds—the fast onset
of lidocaine with the long duration of
action of bupivacaine. However, when
pharmacokinetics is considered, this
practice cannot be recommended. Mixing
LA agents alters the pH and reduces the
concentration gradient and thus affects
onset time, penetration into nerves, and
duration of action. Peer-reviewed reports
also discourage mixing LA agents, and
expert consensus is that “the best of both
worlds” is not achieved. 8,9
cumulative dose that can be administered with sprays.
Neuraxial epidural injections of up to 4 mg/kg in dogs
and cats are generally recommended and are often
combined with morphine (0.1 to 0.2 mg/kg) or
buprenorphine (0.01 to 0.02 mg/kg). Generally, the
maximum recommended volume in dogs is 6 to 7 mL.
Rapid IV injections of 22 mg/kg in dogs and 11 mg/kg
in cats have produced seizures.1 Often, loading doses of
1 to 2 mg/kg IV administered slowly followed by CRI
doses of 10 to 50 µg/kg/min are used in dogs. Due to
the increased risk of toxicity in cats, caution should be
used when considering systemic use of lidocaine in cats.
Administration via syringe pump to allow for more
accurate dosing is generally recommended. If a syringe
pump is not available, lidocaine can be added to a bag
of 0.9% saline for CRI (BOX 2). Lidocaine is light
sensitive; therefore, the fluid bag or syringe should be
kept covered if long-term use is expected.
Take care when using
multiple regional blocks in a
single patient and be aware
that drug absorption varies
between injection sites.
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 PRACTICAL PHARMACOLOGY PEER REVIEWED
BOX 2. Steps to Set Up a Lidocaine
CRI Using a Fluid Pump
Example: Desired infusion rate: 10 µg/kg/
min in a 20-kg dog.
1. Remove 50 mL of 0.9% saline from a 1 L
fluid bag.
2. Add 1000 mg (50 mL) of 2% lidocaine
to the bag to achieve a concentration of
1 mg/mL.
3. Set the fluid pump to run at 12 mL/hr.
CRI = constant rate infusion
Multiple studies have shown the benefits of using
lidocaine–prilocaine topical cream combinations for
reducing pain associated with venipuncture in cats and
dogs when approximately 1 cm2 of the formulation is
applied to the skin overlying the vessel.11,12 However,
care needs to be taken to prevent accidental ingestion.
The hydrolysis of prilocaine releases ortho-toluidine,
which oxidizes hemoglobin and results in clinically
significant methemoglobinemia in children. A study by
Gibbon et al. reported no methemoglobinemia in feline
patients following the use of lidocaine–prilocaine
cream13; however, given that transmucosal and
transdermal absorption are dissimilar, the application of
an occlusive bandage is recommended to decrease the
risk of accidental ingestion. Lidocaine transdermal
patches are available, but evidence supporting their
clinical use in dogs is limited.14,15
Special notes: Lidocaine is classified as a class 1
antiarrhythmogenic drug and can be used to aid in the
treatment of ventricular premature complexes and
ventricular tachycardia. As previously mentioned,
lidocaine may provide effective perioperative analgesia
in dogs, although the mechanism is poorly
understood.16 Additionally, lidocaine may be combined
with opioids (e.g., morphine, fentanyl, methadone)
and/or dissociative anesthetic agents (e.g., ketamine)
for advanced perioperative pain management.
Experimentally in other species (pigs and humans),
lidocaine reduces the concentration of systemic
inflammatory mediators and reduces the risk for
multiorgan dysfunction (MODS) following hypoxic
reperfusion injury.17,18 Lidocaine’s potential benefit for
MODS attenuation during gastrointestinal surgery in
30 MAY/JUNE 2023 todaysveterinarypractice.com
dogs is inconclusive, yet promising. The anesthetic-
sparing effects (minimum alveolar concentration
[MAC] reduction) of lidocaine may only be appreciable
at higher doses (5 to 6 mg/kg/h) and often provide an
insubstantial effect (<20% MAC reduction) compared
with opioids and dissociative anesthetic agents.19,20
Higher doses of lidocaine (12 mg/kg/h) that have
increased MAC reduction generally result in vomiting
and ataxia in recovery.
Lidocaine has been combined with α2 receptor agonists
such as dexmedetomidine to increase the duration
(approximately 300 minutes) of peripheral nerve
blockade in dogs.21 This may be helpful when longer-
acting LA agents such as bupivacaine or ropivacaine are
unavailable or are contraindicated. Care should be
taken when using these formulations (in addition to
commercially available lidocaine–epinephrine
formulations) in regions where collateral circulation is
poor, such as the tail.
Mepivacaine Hydrochloride
Background: Commonly available as a 2% (20 mg/
mL) hydrochloride solution. Mepivacaine has a fast
onset and intermediate duration of action.
Indications: Topical application, local infiltration into
tissues or cavities, and peripheral perineural injection.
Recommended doses and safety: Peripheral perineural
injections of up to 6 mg/kg in dogs and 3 mg/kg in cats
are generally recommended. The perineural dose
reported to cause seizures is 29 mg/kg.1 Mepivacaine
should not be administered intravenously. Intra-
articular doses of 1 to 2 mg/kg are commonly used
clinically.
Special notes: Mepivacaine is considered minimally
chondrotoxic and results in less tissue irritation and
vasodilation than lidocaine or bupivacaine. It is
commonly used for intra-articular and intrasynovial
injections, particularly in horses.
Ropivacaine Hydrochloride
Background: Commonly available as a 0.2% (2 mg/
mL), 0.75% (7.5 mg/mL), or 1% (10 mg/mL)
hydrochloride solution. Ropivacaine has a slow onset
and long duration of action.

Indications: Local infiltration into tissues or cavities,
peripheral perineural injection, and central neuraxial
injection.
Recommended doses and safety: Peripheral perineural
injections of up to 3 mg/kg in dogs and 2 mg/kg in cats
are generally recommended. Ropivacaine should not be
administered intravenously. Neuraxial epidural
injections of up to 1 mg/kg are generally recommended
and are often combined with morphine (0.1 to 0.2 mg/
kg) or buprenorphine (0.01 to 0.02 mg/kg).
Special notes: Ropivacaine is considered the least
chondrotoxic LA agent and is commonly used for
intra-articular and intrasynovial injections. Ropivacaine
has a slightly lower lipophilicity than bupivacaine,
meaning the motor blockade produced by ropivacaine
may be less profound and of shorter duration.22 For this
reason, ropivacaine is the LA agent of choice at the
authors’ institution for the provision of neuraxial
analgesia and peripheral nerve desensitization.
Bupivacaine Hydrochloride
Background: An equimolar racemic mixture of R- and
S-enantiomers commonly available as a 0.25%
(2.5 mg/mL), 0.5% (5 mg/mL), or 0.75% (7.5 mg/
mL) hydrochloride solution. Bupivacaine has a slow
onset and long duration of action.
Indications: Local infiltration into tissues or cavities,
peripheral perineural injection, and central neuraxial
injection.
Recommended doses and safety: Perineural injections
of up to 2 mg/kg are generally recommended in dogs
and cats. Bupivacaine should not be administered
intravenously due to its profound cardiotoxicity.
Compared with lidocaine, bupivacaine causes
significant myocardial depression and
arrhythmogenicity. Epidural injections of up to 1 mg/
kg are generally recommended and are often combined
with morphine (0.1 to 0.2 mg/kg) or buprenorphine
(0.01 to 0.02 mg/kg).
Special notes: Levobupivacaine contains only the
S-enantiomer of the bupivacaine molecule. It is
considered slightly less cardiotoxic; however, IV
administration is still not recommended.
PEER REVIEWED PRACTICAL PHARMACOLOGY
Liposomal encapsulation
delays systemic absorption
and prolongs activity at the
site of injection. Encapsulation
prevents diffusion through
tissue planes until the active
ingredient is released.
Bupivacaine Liposome
Injectable Suspension (BLIS)
Background: BLIS is available as a 13.3 mg/mL
extended-release formulation (Nocita; Elanco,
elanco.us).
Indications: Registered for local infiltration into the
tissue planes following cruciate ligament surgery in
dogs and prior to onychectomy in cats, administered as
a 4-point block.
Recommended doses and safety: Local infiltration of
5.3 mg/kg (0.4 mL/kg) for the provision up to
72 hours of nerve desensitization (analgesia). Sterile
saline can be used to increase the volume to cover the
entire surgical area in dogs. BLIS should not be
administered intravenously or as a neuraxial injection.
Special notes: Reported adverse reactions include
discharge from the incision, incisional inflammation,
proteinuria and vomiting in dogs, and pyrexia in cats.
Liposomal encapsulation delays systemic absorption
and prolongs activity at the site of injection.
Encapsulation prevents diffusion through tissue planes
until the active ingredient is released. Therefore,
effective analgesia outside the tissue plane of injection
is delayed. A detailed review of BLIS has been
published elsewhere.23
SUMMARY
LA agents are affordable and readily available, and they
play an important part of a multimodal analgesic
protocol. Various formulations of LA agents are
available. Toxicity, while generally uncommon, can
occur, and several steps can be implemented to improve
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 PRACTICAL PHARMACOLOGY PEER REVIEWED
patient safety. Additional benefits to locoregional
anesthesia provided by LA agents include opioid-
sparing, balanced anesthesia and improved patient
outcomes. Systemic analgesia, ventricular antiarrythmia
treatment, and MODS attenuation are additional
benefits of IV administration of lidocaine in dogs.
References
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Michelle Ting Hoon
Michelle completed her bachelor of veterinary science
degree at the University of Sydney in 2014. Following
graduation, she practiced as a primary care veterinarian
across multiple states in Australia. Subsequently,
Michelle completed her rotating and anesthesia
internships at the Sydney University Veterinary Teaching
Hospital. She is currently undertaking a residency
program in veterinary anesthesia and analgesia and
her doctor of veterinary clinical science degree at the
University of Queensland. Her interests include small
animal regional anesthesia techniques, pain, and critical
patient management.
Shaun Pratt
Shaun graduated from the University of Queensland. He
completed an anesthesia internship at the University of
Sydney, followed by 2 years working in private general
practice. Shaun returned to the University of Queensland
in 2021 to complete his residency and doctoral training
in anesthesia and analgesia.
Wendy Goodwin
Dr. Goodwin has worked for the University of
Queensland as a clinical anesthetist since 2010. She
received her veterinary degree and doctorate of
philosophy from the University of Queensland and is
a Fellow of the Australian and New Zealand College
of Veterinary Scientists in veterinary anaesthesia and
critical care (registered specialist). Dr. Goodwin is
passionate about veterinary anesthesia and analgesia
and has dedicated her professional career to pursuing
excellence in this field. Her clinical anesthetic experience
has covered a wide range of species, including horses,
small animal companion animals, farm animals, avian and
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